Quantitative Fundus Autofluorescence in Retinal Disorders

视网膜疾病中的定量眼底自发荧光

• 批准号: 9084593
• 负责人: Janet Ruthe Sparrow
• 金额: $ 45.47万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9084593
• 关键词: Address; Affect; Age; Age related macular degeneration; Alleles; Biological; Carrier State; Cells; Chemicals; Clinical; Complex; Complex Mixtures; Data; Deposition; Diagnosis; Disease; Disease Progression; Epithelial; Ethnic Origin; Etiology; Exhibits; Eye; Flecks; Fundus; Gender; Genetic; Genotype; Health; Image; Individual; Influentials; Investigation; Lasers; Legal Blindness; Light; Link; Lipofuscin; Longitudinal Studies; Measurement; Measures; Methods; Monitor; Mutation; Normal Range; Ophthalmoscopy; Optics; Participant; Pathogenesis; Patients; Pattern; Phagocytosis; Phenotype; Photoreceptors; Physics; Pigments; Positioning Attribute; Process; Research Personnel; Retina; Retinal; Retinal Degeneration; Retinal Diseases; Retinal Pigments; Retinaldehyde; Retinitis Pigmentosa; Scanning; Sparrows; Stargardt' s disease; Structure of retinal pigment epithelium; Susceptibility Gene; Testing; Variant; Work; aged; base; clinical phenotype; cohort; early onset; fluorophore; follow-up; human disease; macular dystrophy; pattern dystrophies; risk variant; therapy outcome

DESCRIPTION (provided by applicant): The inherent autofluorescence (AF) of the fundus originates from RPE lipofuscin. While RPE lipofuscin is amassed even in healthy eyes, homozygous mutations in ABCA4 are well known to confer accelerated formation of these fluorophores. Moreover, imaging of fundus AF by confocal scanning laser ophthalmoscopy (cSLO) has shown that the patterns and intensities of AF deviate from normal in several retinal disorders. Thus we aim to demonstrate that a standardized approach to quantifying fundus AF (qAF) can assist in the diagnosis of retinal disease, in the monitoring of disease progression and in the assessment of therapeutic outcomes. To enable this investigation we have gathered normative qAF data from a large number of participants with healthy eye status (aged 6-60) so as to establish ranges of qAF values with respect to age, gender and ethnicity. Going forward we will use these normal values to examine for genotype/phenotype correlations between specific ABCA4 alleles and fundus AF levels (qAF) in patients diagnosed with ABCA4- associated disease (Aim 1.1). In longitudinal studies we will measure changes in qAF values after 1 and 2 year follow-up of ABCA4-affected individuals (Aim 1.2). We will determine whether the carrier state (heterozygous) of ABCA4 is associated with elevated RPE lipofuscin, the latter being measured as qAF and compared to age-matched normals (Aim 1.3). We will also investigate the cellular basis of retinal flecks (Aim 1.4). In Aim 2, we will determine whether the quantification of fundus SW-AF can aid in differentiating between pattern dystrophy (PD) associated with PRPH2/RDS mutations versus similar phenotypes observed with ABCA4 variants (Aim 2.1). We will also compare qAF values in individuals presenting with bull's eye macular dystrophy that is of ABCA4- versus non-ABCA4 origin (Aim 2.2). In patients with RP, we will measure qAF over the autofluorescent rings that are often a feature of this disorder. qAF Intensities inside, within and outside the rings will be compared to levels in our normal controls so as to further the use of fundus AF imaging to monitor disease progression in RP. In Aim 4, we will determine whether elevated fundus AF is a factor influencing the onset and progression of AMD when controlling for specific CFH and ARMS2 alleles. In summary, the studies proposed in this application will examine the contribution that the lipofuscin of retina makes to the onset and progression of several retinal diseases and will demonstrate that quantitation of fundus AF facilitates the diagnosis and monitoring of some retinal disorders.

描述（由申请人提供）：底眼的固有自动荧光（AF）源自RPE脂肪霉素。尽管即使在健康的眼睛中也会积聚RPE脂肪霉素，但众所周知，ABCA4中的纯合突变是赋予这些荧光团加速形成的众所周知。此外，通过共聚焦扫描激光眼镜检查（CSLO）对眼底AF的成像表明，在几种视网膜疾病中，AF的模式和强度偏离了正常状态。因此，我们旨在证明量化眼底AF（QAF）的标准化方法可以帮助诊断视网膜疾病，监测疾病进展和评估治疗结果。为了实现这项调查，我们收集了来自大量具有健康眼睛状态的参与者（6-60岁）的规范性QAF数据，以建立QAF值范围的年龄，性别和种族。展望未来，我们将使用这些正常值检查特定ABCA4等位基因和基底AF水平（QAF）之间的基因型/表型相关性，该患者被诊断出患有ABCA4相关疾病（AIM 1.1）。在纵向研究中，我们将测量1年和2年受ABCA4影响个体的随访后QAF值的变化（AIM 1.2）。我们将确定ABCA4的载体状态（杂合）是否与升高的RPE脂肪霉素有关，后者被测量为QAF，并与年龄匹配的正态相比（AIM 1.3）。我们还将研究视网膜斑点的细胞基础（AIM 1.4）。在AIM 2中，我们将确定是否 基底SW-AF的量化可以帮助区分与PRPH2/RDS突变相关的模式营养不良（PD）与ABCA4变体观察到的类似表型相关的模式营养不良（PD）（AIM 2.1）。我们还将比较出现的个体中的QAF值，该个体与Bull's Eye Basular营养不良症（ABCA4-与非ABCA4起源）相比（AIM 2.2）。在RP患者中，我们将测量通常是这种疾病特征的自动荧光环上的QAF。将环内外的QAF强度与我们正常对照中的水平进行比较，以进一步使用基底AF成像来监测RP中的疾病进展。在AIM 4中，我们将确定升高的基底AF是否是控制特定CFH和Arms2等位基因时AMD发作和进展的因素。总而言之，本申请中提出的研究将研究视网膜脂蛋白对几种视网膜疾病的发作和进展的贡献，并将证明对基底AF的定量促进了某些视网膜疾病的诊断和监测。